Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study

Ocular Hypertension Treatment Study

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Abstract

Purpose: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). Design: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. Methods: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. Results: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. Conclusion: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalAmerican Journal of Ophthalmology
Volume199
DOIs
StatePublished - Mar 1 2019

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Ocular Hypertension
Incidence
Risk Reduction Behavior
Confidence Intervals
Primary Open Angle Glaucoma
Comorbidity
Observation

ASJC Scopus subject areas

  • Ophthalmology

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Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study. / Ocular Hypertension Treatment Study.

In: American Journal of Ophthalmology, Vol. 199, 01.03.2019, p. 193-199.

Research output: Contribution to journalArticle

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title = "Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study",
abstract = "Purpose: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). Design: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. Methods: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. Results: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58{\%} (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5{\%} and 13.2{\%}, respectively, in the observation group and 13.1{\%} and 5.8{\%}, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33{\%} reduction in risk (relative risk = 0.67, 95{\%} confidence interval [CI] of 0.54-0.84) and a 56{\%} reduction in risk for POAG endpoints (relative risk = 0.44, 95{\%} CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. Conclusion: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23{\%}. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.",
author = "{Ocular Hypertension Treatment Study} and Gordon, {Mae O.} and Higginbotham, {Eve J.} and Heuer, {Dale K.} and Parrish, {Richard K} and Robin, {Alan L.} and Morris, {Patricia A.} and Dunn, {Deborah A.} and Wilson, {Bradley S.} and Kass, {Michael A.}",
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T1 - Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study

AU - Ocular Hypertension Treatment Study

AU - Gordon, Mae O.

AU - Higginbotham, Eve J.

AU - Heuer, Dale K.

AU - Parrish, Richard K

AU - Robin, Alan L.

AU - Morris, Patricia A.

AU - Dunn, Deborah A.

AU - Wilson, Bradley S.

AU - Kass, Michael A.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Purpose: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). Design: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. Methods: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. Results: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. Conclusion: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.

AB - Purpose: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). Design: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. Methods: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. Results: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. Conclusion: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.

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